The present invention relates to treatment of damaged cardiac tissue.
Cardiovascular disease is a leading cause of death in the United States, and heart failure is a major public health problem in the United States. Gene therapy may provide promising new therapies for this vexing public health problem. However, gene delivery is the most important as yet unsolved problem limiting the applicability of gene therapy for the treatment of heart failure. This applies equally to heart failure due to defined X-linked or autosomal recessive gene defects and to the more common forms of heart failure without a well-defined genetic basis since promising vectors and therapeutic transgenes have been identified for both.
Bridges et al., Annals of Thoracic Surgery, 73: 1939-1946 (2002) describe a cardiopulmonary surgical technique for a so-called “incomplete isolation” of a subject's heart in situ. The cardiac isolation technique requires the formation of two separate cardiopulmonary bypass circuits, one for systemic circulation of the body and one for antegrade cardiac circulation of a gene delivery vector. The technique enables multiple passes, or recirculation, of a macromolecular complex through a subject's heart during cardiopulmonary bypass surgery.
A technique which isolates the heart to permit systemic delivery of genes is described in International Publication No. WO 2005/030292 (Apr. 7, 2005), and its corresponding U.S. national phase application Ser. No. 10/573,129. In addition, a balloon catheter useful in retrograde perfusion of the heart with drugs, gene therapy vectors or other solutions via the coronary sinus is described in U.S. patent application Ser. No. 10/572,238 and its corresponding International Publication No. WO 2005/027995, published Mar. 31, 2005.
A cardiac isolation circuit has been described for use in delivery of macromolecular complexes. See, e.g., International Patent Application No. PCT/US2005/34283, published as WO 2006/039218.
There is need for new methods for treating cardiac injury and disease.